The secretion of growth hormone (GH) is controlled by two hypothalamic peptides; somatostatin, which inhibits GH; and growth-hormone releasing factor (GRF), which stimulates GH. Within the past year, GRF has been isolated, sequenced, and synthesized. We are using GRF as a tool to study the physiology of the neuroendocrine regulation of GH, and exploring the potential uses of GRF in the diagnosis and treatment of diseases including GH deficiency (dwarfism) and GH excess (gigantism and acromegaly). We initially tested the biological activities of GRF in vivo and in vitro, determined its safety in animal studies, and began to develop accurate assays for GRF, preparatory to clinical studies in patients and normal volunteers. Results to date have shown that the actions of GRF are potent and highly specific in vitro, stimulating only GH in a dose-dependent fashion in perifused pituitary cells. GRF is also active in humans, stimulating a prompt elevation of GH in normal men and women, with few side effects. The dose-response curve for these effects in adult men and women has been delineated. A third of adult subjects with growth hormone deficiency respond to GRF with a rise in GH. This suggests that idiopathic GH deficiency can be due to a deficiency in hypothalamic GRF. This finding has two implications: first, that GRF testing may be a useful alternative to other diagnostic tests of GH function, and second, that repetitive stimulation with GRF could potentially be used to treat GRF deficient growth failure. In support of this possibility, we have administered GRF repeatedly over 5 days and shown a rise in somatomedin-C, which mediates many of the effects of GH on growth. We have recently extended these studies to GH-deficient children. We have shown that most patients with acromegaly (GH-producing pituitary tumors) respond to GRF, a finding which suggests that GRF antagonists might be effective treatment for this disorder. We have established assays for GRF using both traditional RIA and ELISA techniques. GRF appears to have low antigenicity in the few human studies to date.